Abstract
AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.
Keywords: COVID-19; Coronavirus; Fc-fusion; Infectious disease; Pandemic; Prophylaxis.
【저자키워드】 COVID-19, coronavirus, pandemic, Infectious disease, Prophylaxis, Fc-fusion, 【초록키워드】 viral infection, Vaccine, immunogenicity, Clinical symptoms, B.1.351, neutralization, COVID-19 pandemic, Infection, SARS-CoV-2 virus, adjuvants, Infectious disease, virus, Spike protein, Receptor binding domain, Antigen, Prophylaxis, Region, Viral, cells, mice, non-human primates, NHPs, African, Clinical studies, Subunit vaccine, adjuvant, receptor, virus infection, fusion protein, non-human primate, viral variant, single dose, Neutralizing titer, preclinical study, clinical study, dose, phase, Neonatal, preclinical studies, viral strain, Support, viral spike protein, APCS, subunit, clinical symptom, clinical development, live SARS-CoV-2, immunogenic, South, augmentation, doses, FcγR, USA-WA1/2020, IgG titers, expectation, Vero-E6 cells, SARS-CoV-2 viral infection, NHP, Cell, human IgG1 Fc, huACE2, ENhance, greater, evaluated, maintain, comparable, K18, neutralizing IgG titer, the SARS-CoV-2, 【제목키워드】 Vaccine, development, subunit,